A combinatorial phage display library for the generation of specific Fab fragments recognizing human spermatozoa and inhibiting fertilizing capacity in vitro

To select a source of lymphocytes for the generation of an anti-sperm-biased combinatorial phage display library, venous blood was obtained from 34 vasovasostomy (vasectomy reversal) patients approximately 3 mo after surgery. Using a variety of immunoassays, serum was analyzed for antibodies against human spermatozoa, and a patient was selected on the basis of high titer of antibodies that recognized the equatorial region of the sperm head and inhibited sperm fertilizing capacity in vitro. Total RNA isolated from the stored lymphocytes of this individual was reversed transcribed, and gamma1 (Fd) region and kappa chains were amplified by polymerase chain reaction for the successful construction of an antibody phage display library. The library was panned against human spermatozoa to isolate sperm-specific phage that recognized the equatorial region of the sperm head. Three preparations of Fab were tested via the hamster egg penetration test. Each preparation significantly (p < 0. 005) inhibited sperm-egg binding and fusion, with one preparation (designated Fab-G) causing complete inhibition. Sequence analysis of the kappa light gene encoding Fab-G revealed a 93% homology with the light chain of human anti-human immunodeficiency virus gp120 p35 variable region. This technology may have a practical application in characterization of the immune response to spermatozoa and for the design of sperm-based contraceptive vaccines.     

Aorto-iliac thrombosis in a foal

A six-day-old Missouri foxtrotter colt was examined because it had had diarrhoea since it was 24 hours old. A diagnosis of colitis, septicaemia, and disruption of the arterial blood flow to the pelvic limbs was made on the basis of clinical and laboratory findings. Despite intensive medical therapy, the foal died 13 hours after being examined. Postmortem examination revealed diffuse fibrinous enteritis with lymphoid necrosis, multifocal fibrinonecrotic typhlocolitis, disseminated intravascular coagulation, and a large occluding thrombus at the aortic termination. The results of bacteriological culturing supported the diagnosis of septicaemia leading to activation of the clotting cascade, disseminated intravascular coagulation, aorto-iliac thrombosis and infarction of the pelvic limbs.     

1998 William J. Stickel Bronze Award. Antifungal activity of Melaleuca alternifolia (tea-tree) oil against various pathogenic organisms

Tea-tree oil (oil of Melaleuca alternifolia) has recently received much attention as a natural remedy for bacterial and fungal infections of the skin and mucosa. As with most naturally occurring agents, claims of effectiveness have been only anecdotal; however, several published studies have recently demonstrated tea-tree oil's antibacterial activity. This study was conducted to determine the activity of tea-tree oil against 58 clinical isolates: Candida albicans (n = 10), Trichophyton rubrum (n = 8), Trichophyton mentagrophytes (n = 9), Trichophyton tonsurans (n = 10), Aspergillus niger (n = 9), Penicillium species (n = 9), Epidermophyton floccosum (n = 2), and Microsporum gypsum (n = 1). Tea-tree oil showed inhibitory activity against all isolates tested except one strain of E floccosum. These in vitro results suggest that tea-tree oil may be useful in the treatment of yeast and fungal mucosal and skin infections.     

The effects of instructional match and content overlap on generalized reading performance

This study examined the effects of instructional match and content overlap on students' ability to generalize from passage reading instruction. Four students with mild disabilities served as participants. Using a multielement design, students were instructed with passages at two levels of text difficulty (instructionally matched vs. instructionally mismatched), and generalization was assessed with passages at two levels of similarity to those instructed (low vs. high content overlap). Results indicated that students' oral reading accuracy and fluency showed the greatest degree of generalization when instructional materials were matched to the students' skill level and assessment materials were similar to those used during instruction. Moreover, these results were maintained at 1-month follow-up. The implications of these findings for classroom reading instruction and the assessment of students' reading skills are discussed.     

Covering a string

We consider the problem of finding the repetitive structures of a given stringx. The periodu of the stringx grasps the repetitiveness ofx, sincex is a prefix of a string constructed by concatenations ofu. We generalize the concept of repetitiveness as follows: A stringw covers a stringx if there is a superstring ofx which is constructed by concatenations and superpositions ofw. A substringw ofx is called aseed ofx ifw coversx. We present anO(n logn)-time algorithm for finding all the seeds of a given string of lengthn.Partially supported by SERC Grants GR/F 00898 and GR/J 17844, NATO Grant CRG 900293, ESPRIT BRA Grant 7131 for ALCOMII, and MRC Grant G 9115730.Partially supported by MRC Grant G 9115730 and S.N.U. Posco Research Fund 94-15-1112.     

Severe progressive deformities after limb lengthening in type-II fibular hemimelia

Until recently the accepted treatment of choice for severe type-II fibular hemimelia has been Syme's or Boyd's amputation. The alternative of distraction lengthening using the Ilizarov technique is now available. We report three patients (four limbs) with type-II fibular hemimelia who were treated by the Ilizarov technique and followed up for two to six years. Severe progressive procurvatum and valgus deformity of the tibia and valgus deformity and lateral subluxation of the ankle were found in all four limbs. Multiple additional soft-tissue and bony surgery was necessary. In view of these problems we feel that reappraisal of the indications for lengthening in type-II fibular hemimelia is necessary.     

The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study

1. We have studied the effects of muscarinic cholinoceptor agonists and subtype-preferring antagonists on the isometric contraction of smooth muscle strips from dog prostate. 2. Acetylcholine and carbachol induced contraction of prostate strips from the peripheral zone, ('the capsule'). Bethanechol contracted the tissue but not at lower doses. McN-A-343 and oxotremorine-M showed the same effects. 3. Blocking alpha- and beta-adrenoceptors with phentolamine and propranolol, respectively, did not modify carbachol-induced contractions. 4. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M) did not affect the contractile response evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic receptor antagonist, atropine (10(-11)-10(-9) M), inhibited it in a competitive manner. 5. The muscarinic M1 (pirenzepine), M2 [AF-DX 116, himbacine (M2/M4) and methoctramine], M3 (HHSID and f-F-HHSID), and putative M4 (tropicamide) antagonists reduced significantly the carbachol-induced contractions. The pIC50 values were: atropine (10.01) > himbacine (8.3) > methoctramine (7.85) > AF-DX 116 (7.60) > HHSID (7.21) > p-F-HHSID (7.10) > pirenzepine (7.30) > tropicamide (7.00). 6. The antagonist profile indicates that an predominant M2 receptor subtype could mediate the muscarinic contraction in the canine prostate.     

Constrained length minimum inductance gradient coil design

A gradient coil design algorithm capable of controlling the position of the homogeneous region of interest (ROI) with respect to the current-carrying wires is required for many advanced imaging and spectroscopy applications. A modified minimum inductance target field method that allows the placement of a set of constraints on the final current density is presented. This constrained current minimum inductance method is derived in the context of previous target field methods. Complete details are shown and all equations required for implementation of the algorithm are given. The method has been implemented on computer and applied to the design of both a 1:1 aspect ratio (length:diameter) central ROI and a 2:1 aspect ratio edge ROI gradient coil. The 1:1 design demonstrates that a general analytic method can be used to easily obtain very short gradient coil designs for use with specialized magnet systems. The edge gradient design demonstrates that designs that allow imaging of the neck region with a head sized gradient coil can be obtained, as well as other applications requiring edge-of-cylinder regions of uniformity.     

Susceptibility of penicillin-susceptible and -resistant pneumococci to CFC-222, a new fluoroquinolone

Rotavirus (RV) strains infecting newborns often have unique neutralization antigens (P serotypes) on their outer capsids that are distinct from those found on RV strains that cause diarrhea in older children. We examined the hypothesis that unusual RV strains preferentially infect newborns because the newborns lack maternal neutralizing antibodies to these strains. To test this hypothesis, sera and saliva samples collected from neonates infected with 116E-like (P[11]G9) strains in the maternity ward of the All India Institute of Medical Sciences (AIIMS) hospital in New Delhi were tested for neutralizing antibodies against common RV strains and those infecting newborns and these titers were compared with those of newborns who did not become infected (controls). The infected neonates had significantly lower levels of cord blood neutralizing antibodies to 116E than the controls, suggesting that immunity to neonatal RV infection is acquired transplacentally through maternal antibodies. Further, this study confirmed the immunogenicity of the AIIMS neonatal strain 116E, a vaccine candidate, in its ability to evoke a potent RV-specific immunoglobulin A and neutralizing antibody response in serum and saliva among the infected babies. Our findings have important implications for the development of an effective RV vaccine. In India, where G9 strains are common in the community, the use of 116E as a vaccine, together with the rhesus tetravalent vaccine, may provide a broader protection against all the circulating RV serotypes, including serotype G9, which is not represented in the current rhesus RV tetravalent vaccine (G1-G4).